Transforming Growth Factor Beta 3 Is Required for Excisional Wound Repair In Vivo

Wound healing is a complex process that relies on proper levels of cytokines and growth factors to successfully repair the tissue. Of particular interest are the members of the transforming growth factor family. There are three TGF-beta isoforms-TGF beta 1, 2, and 3, each isoform showing a unique expression pattern, suggesting that they each play a distinct function during development and repair. Previous studies reported an exclusive role for TGF-beta 3 in orofacial development and a potent anti-scarring effect. However, the role of TGF-beta 3 in excisional wound healing and keratinocyte migration remains poorly understood. We tested the effect of TGF-beta 3 levels on excisional cutaneous wounds in the adult mouse by directly injecting recombinant TGF-beta 3 or neutralizing antibody against TGF-beta 3 (NAB) in the wounds. Our results demonstrate that TGF-beta 3 does not promote epithelialization. However, TGF-beta 3 is necessary for wound closure as wounds injected with neutralizing antibody against TGF-beta 3 showed increased epidermal volume and proliferation in conjunction with a delay in keratinocyte migration. Wild type keratinocytes treated with NAB and Tgfb3-deficient keratinocytes closed an in vitro scratch wound with no delay, suggesting that our in vivo observations likely result from a paracrine effect.